Limb- and Person-Level Risk Factors for Lower-Limb Amputation in the Prospective Seattle Diabetic Foot Study

Diabetes is the leading cause of nontraumatic lower-limb amputations in the U.S., but no research has prospectively examined associations between limb-specific measurements and amputation risk among patients without foot ulcer. We investigated amputation risk by limb in relation to the same limb- and person-level factors.

We conducted a 22-year prospective study among 1,461 male patients with diabetes without foot ulcer (mean age 62.4 years), with 2,893 lower limbs among subjects recruited between 1990 and 2002 from one Department of Veterans Affairs general internal medicine clinic. The following information was collected: demographic, lifestyle, and diabetes characteristics; visual acuity; kidney function (estimated glomerular filtration rate [eGFR]); and lower-limb measurements including presence of Charcot deformity, sensory neuropathy by 10-g monofilament, dorsal foot transcutaneous oximetry (TcPO₂) at 44°C, and ankle-brachial index (ABI).

Over 25,735 limb-years, 136 amputations occurred. A multivariable Cox model identified multiple independent risk factors: sensory neuropathy (hazard ratio 3.09 [95% CI 2.02-4.74]), ABI ≤0.5 vs. >0.9 to <1.3 (3.98 [2.31-6.85]), ABI ≥1.3 vs. >0.9 to <1.3 (2.20 [1.18-4.09]), 1-SD decrease in eGFR (1.18 [1.00-1.38]), poor vision (1.70 [1.05-2.73]), body weight in 21.4-kg increments (0.78 [0.61-0.98]), and age >70 years vs. <57 years (0.13 [0.04-0.38]). Although TcPO₂ was not significantly associated with amputation overall, TcPO₂ <26 mmHg significantly predicted a higher risk in the ABI ≥1.3 category.

Arterial disease and neuropathy emerged as the only limb-specific risk factors for amputation, but these and several person-level factors may be amenable to prevention or treatment interventions to potentially reduce diabetic amputation risk.